Dimensions of professional competences for interventions towards sustainability

This paper investigates sustainability competences through the eyes of professional practitioners in the field of sustainability and presents empirical data that have been created using an action research approach. The design of the study consists of two workshops, in which professional practitioners in interaction with each other and the facilitators are invited to explore and reflect on the specific knowledge, skills, attitudes and behaviours necessary to conduct change processes successfully towards sustainability in a variety of business and professional contexts. The research focuses on the competences associated with these change processes to devise, propose and conduct appropriate interventions that address sustainability issues. Labelled ‘intervention competence’, this ability comprises an interlocking set of knowledge, skills, attitudes and behaviours that include: appreciating the importance of (trying to) reaching decisions or interventions; being able to learn from lived experience of practice and to connect such learning to one’s own scientific knowledge; being able to engage in political-strategic thinking, deliberations and actions, related to different perspectives; the ability for showing goal-oriented, adequate action; adopting and communicating ethical practices during the intervention process; being able to cope with the degree of complexity, and finally being able to translate stakeholder diversity into collectively produced interventions (actions) towards sustainability. Moreover, this competence has to be practised in contexts of competing values, non-technical interests and power relations. The article concludes with recommendations for future research and practice

Utilizing international networks for accelerating research and learning in transformational sustainability science

A promising approach for addressing sustainability problems is to recognize the unique conditions of a particular place, such as problem features and solution capabilities, and adopt and adapt solutions developed at other places around the world. Therefore, research and teaching in international networks becomes critical, as it allows for accelerating learning by sharing problem understandings, successful solutions, and important contextual considerations. This article identifies eight distinct types of research and teaching collaborations in international networks that can support such accelerated learning. The four research types are, with increasing intensity of collaboration: (1) solution adoption; (2) solution consultation; (3) joint research on different problems; and (4) joint research on similar problems. The four teaching types are, with increasing intensity of collaboration: (1) adopted course; (2) course with visiting faculty; (3) joint course with traveling faculty; and (4) joint course with traveling students. The typology is illustrated by extending existing research and teaching projects on urban sustainability in the International Network of Programs in Sustainability, with partner universities from Europe, North America, Asia, and Africa. The article concludes with challenges and strategies for extending individual projects into collaborations in international networks.Postprint (author's final draft

The Association of the Metabolic Syndrome with PAI-1 and t-PA Levels

Background. We used a random sample (n = 2, 495) from the population-based Prevention of Renal and Vascular End-stage Disease (PREVEND) study population to examine the association of the metabolic syndrome (Met S) with plasminogen activator inhibitor type 1 (PAI-1) and tissue plasminogen activator (t-PA) antigen levels. Results. The overall prevalence of the Met S was 18%, was dependent on age and gender, and was positively associated with higher antigen levels of both PAI-1 and t-PA. These significant effects were maintained after adjustment for age, gender, BMI, elevated C-reactive protein, smoking status, urinary albumin excretion, and insulin levels. We found no significant interactions between the Met S and other covariates on PAI-1 and t-PA levels. Conclusions. Our study demonstrates that those with the Met S have significantly higher levels of PAI-1 and t-PA antigen, factors known to increase the risk of cardiovascular disease

Complementation of hypersensitivity to DNA interstrand crosslinking agents demonstrates that XRCC2 is a Fanconi anaemia gene

Background Fanconi anemia (FA) is a heterogeneous inherited disorder clinically characterized by progressive bone marrow failure, congenital anomalies, and a predisposition to malignancies. Objective Determine, based on correction of cellular phenotypes, whether XRCC2 is a FA gene. Methods Cells (900677) from a previously identified patient with biallelic mutation of XRCC2, among other mutations, were genetically complemented with wild-type XRCC2. Results Wild-type XRCC2 corrects each of three phenotypes characteristic of FA cells, all related to the repair of DNA interstrand crosslinks, including increased sensitivity to mitomycin C (MMC), chromosome breakage, and G2-M accumulation in the cell cycle. Further, the p.R215X mutant of XRCC2, which is harbored by the patient, is unstable. This provides an explanation for the pathogenesis of this mutant, as does the fact that 900677 cells have reduced levels of other proteins in the XRCC2-RAD51B-C-D complex. Also, FANCD2 monoubiquitination and foci formation, but not assembly of RAD51 foci, are normal in 900677 cells. Thus, XRCC2 acts late in the FA-BRCA pathway as also suggested by hypersensitivity of 900677 cells to ionizing radiation. These cells also share milder sensitivities toward olaparib and formaldehyde with certain other FA cells. Conclusions XRCC2/FANCU is a FA gene, as is another RAD51 paralog gene, RAD51C/FANCO. Notably, similar to a subset of FA genes that act downstream of FANCD2, biallelic mutation of XRCC2/FANCU has not been associated with bone marrow failure. Taken together, our results yield important insights into phenotypes related to FA and its genetic origins

Fibroblast Growth Factor 23 and Risk of New Onset Heart Failure With Preserved or Reduced Ejection Fraction:The PREVEND Study

Background The role of fibroblast growth factor 23 (FGF23) in the development of new-onset heart failure (HF) with reduced (HFrEF) or preserved ejection fraction (HFpEF) in the general population is unknown. Therefore, we set out to investigate associations of C-terminal FGF23 with development of new-onset HF and, more specifically, with HFrEF or HFpEF in a large, prospective, population-based cohort. Methods and Results We studied 6830 participants (aged 53.8 +/- 12.1 years; 49.7% men; estimated glomerular filtration rate, 93.1 +/- 15.7 mL/min per 1.73 m(2)) in the community-based PREVEND (Prevention of Renal and Vascular End-Stage Disease) study who were free of HF at baseline. Cross-sectional multivariable linear regression analysis showed that ferritin (standardized beta, -0.24; P= 50%). After median follow-up of 7.4 [IQR 6.9-7.9] years, 227 individuals (3.3%) developed new-onset HF, of whom 132 had HFrEF and 88 had HFpEF. A higher FGF23 level was associated with an increased risk of incident HF (fully adjusted hazard ratio, 1.29 [95% CI, 1.06-1.57]) and with an increased risk of incident HFrEF (fully adjusted hazard ratio, 1.31 [95% CI, 1.01-1.69]). The association between FGF23 and incident HFpEF lost statistical significance after multivariable adjustment (hazard ratio, 1.22 [95% CI, 0.87-1.71]). Conclusions Higher FGF23 is independently associated with new-onset HFrEF in analyses fully adjusted for cardiovascular risk factors and other potential confounders. The association between FGF23 and incident HFpEF lost statistical significance upon multivariable adjustment

Age dependent associations of risk factors with heart failure:pooled population based cohort study

OBJECTIVE: To assess age differences in risk factors for incident heart failure in the general population. DESIGN: Pooled population based cohort study. SETTING: Framingham Heart Study, Prevention of Renal and Vascular End-stage Disease Study, and Multi-Ethnic Study of Atherosclerosis. PARTICIPANTS: 24 675 participants without a history of heart failure stratified by age into young (<55 years; n=11 599), middle aged (55-64 years; n=5587), old (65-74 years; n=5190), and elderly (≥75 years; n=2299) individuals. MAIN OUTCOME MEASURE: Incident heart failure. RESULTS: Over a median follow-up of 12.7 years, 138/11 599 (1%), 293/5587 (5%), 538/5190 (10%), and 412/2299 (18%) of young, middle aged, old, and elderly participants, respectively, developed heart failure. In young participants, 32% (n=44) of heart failure cases were classified as heart failure with preserved ejection fraction compared with 43% (n=179) in elderly participants. Risk factors including hypertension, diabetes, current smoking history, and previous myocardial infarction conferred greater relative risk in younger compared with older participants (P for interaction <0.05 for all). For example, hypertension was associated with a threefold increase in risk of future heart failure in young participants (hazard ratio 3.02, 95% confidence interval 2.10 to 4.34; P<0.001) compared with a 1.4-fold risk in elderly participants (1.43, 1.13 to 1.81; P=0.003). The absolute risk for developing heart failure was lower in younger than in older participants with and without risk factors. Importantly, known risk factors explained a greater proportion of overall population attributable risk for heart failure in young participants (75% v 53% in elderly participants), with better model performance (C index 0.79 v 0.64). Similarly, the population attributable risks of obesity (21% v 13%), hypertension (35% v 23%), diabetes (14% v 7%), and current smoking (32% v 1%) were higher in young compared with elderly participants. CONCLUSIONS: Despite a lower incidence and absolute risk of heart failure among younger compared with older people, the stronger association and greater attributable risk of modifiable risk factors among young participants highlight the importance of preventive efforts across the adult life course

Unravelling the Difference Between Men and Women in Post-CABG Survival

OBJECTIVES: Women have a worse prognosis after coronary artery bypass grafting (CABG) surgery compared to men. We sought to quantify to what extent this difference in post-CABG survival could be attributed to sex itself, or whether this was mediated by difference between men and women at the time of intervention. Additionally, we explored to what extent these effects were homogenous across patient subgroups. METHODS: Time to all-cause mortality was available for 102,263 CABG patients, including 20,988 (21%) women, sourced through an individual participant data meta-analysis of five cohort studies. Difference between men and women in survival duration was assessed using Kaplan–Meier estimates, and Cox’s proportional hazards model. RESULTS: During a median follow-up of 5 years, 13,598 (13%) patients died, with women more likely to die than men: female HR 1.20 (95%CI 1.16; 1.25). We found that differences in patient characteristics at the time of CABG procedure mediated this sex effect, and accounting for these resulted in a neutral female HR 0.98 (95%CI 0.94; 1.02). Next we performed a priori defined subgroup analyses of the five most prominent mediators: age, creatinine, peripheral vascular disease, type 2 diabetes, and heart failure. We found that women without peripheral vascular disease (PVD) or women aged 70+, survived longer than men (interaction p-values 0.04 and 6 × 10–5, respectively), with an effect reversal in younger women. CONCLUSIONS: Sex differences in post-CABG survival were readily explained by difference in patient characteristics and comorbidities. Pre-planned analyses revealed patient subgroups (aged 70+, or without PVD) of women that survived longer than men, and a subgroup of younger women with comparatively poorer survival

Unravelling the Difference Between Men and Women in Post-CABG Survival

OBJECTIVES: Women have a worse prognosis after coronary artery bypass grafting (CABG) surgery compared to men. We sought to quantify to what extent this difference in post-CABG survival could be attributed to sex itself, or whether this was mediated by difference between men and women at the time of intervention. Additionally, we explored to what extent these effects were homogenous across patient subgroups. METHODS: Time to all-cause mortality was available for 102,263 CABG patients, including 20,988 (21%) women, sourced through an individual participant data meta-analysis of five cohort studies. Difference between men and women in survival duration was assessed using Kaplan–Meier estimates, and Cox’s proportional hazards model. RESULTS: During a median follow-up of 5 years, 13,598 (13%) patients died, with women more likely to die than men: female HR 1.20 (95%CI 1.16; 1.25). We found that differences in patient characteristics at the time of CABG procedure mediated this sex effect, and accounting for these resulted in a neutral female HR 0.98 (95%CI 0.94; 1.02). Next we performed a priori defined subgroup analyses of the five most prominent mediators: age, creatinine, peripheral vascular disease, type 2 diabetes, and heart failure. We found that women without peripheral vascular disease (PVD) or women aged 70+, survived longer than men (interaction p-values 0.04 and 6 × 10(–5), respectively), with an effect reversal in younger women. CONCLUSION: Sex differences in post-CABG survival were readily explained by difference in patient characteristics and comorbidities. Pre-planned analyses revealed patient subgroups (aged 70+, or without PVD) of women that survived longer than men, and a subgroup of younger women with comparatively poorer survival

The Development and Subsequent Elimination of Aberrant Peripheral Axon Projections in Semaphorin3A Null Mutant Mice

AbstractSemaphorin3A (previously known as Semaphorin III, Semaphorin D, or collapsin-1) is a member of the semaphorin gene family, many of which have been shown to guide axons during nervous system development. Semaphorin3A has been demonstrated to be a diffusible chemorepulsive molecule for axons of selected neuronal populations in vitro. Analysis of embryogenesis in two independent lines of Semaphorin3A knockout mice support the hypothesis that this molecule is an important guidance signal for neurons of the peripheral nervous system (M. Taniguchi et al., 1997, Neuron 19, 519–530; E. Ulupinar et al., 1999, Mol. Cell. Neurosci. 13, 281–292). Surprisingly, newborn Semaphorin3A null mutant mice exhibit no significant abnormalities (O. Behar et al., 1996, Nature 383, 525–528). In this study we have tested the hypothesis that guidance abnormalities that occurred during early stages of Semaphorin3A null mice development are corrected later in development. We have found that the extensive abnormalities formed during early developmental stages in the peripheral nervous system are largely eliminated by embryonic day 15.5. We demonstrate further that at least in one distinct anatomical location these abnormalities are mainly the result of aberrant projections. In conclusion, these findings suggest the existence of correction mechanisms that eliminate most sensory axon pathfinding errors early in development

Health systems strengthening to arrest the global disability burden: Empirical development of prioritised components for a global strategy for improving musculoskeletal health

Introduction Despite the profound burden of disease, a strategic global response to optimise musculoskeletal (MSK) health and guide national-level health systems strengthening priorities remains absent. Auspiced by the Global Alliance for Musculoskeletal Health (G-MUSC), we aimed to empirically derive requisite priorities and components of a strategic response to guide global and national-level action on MSK health. Methods Design: mixed-methods, three-phase design. Phase 1: qualitative study with international key informants (KIs), including patient representatives and people with lived experience. KIs characterised the contemporary landscape for MSK health and priorities for a global strategic response. Phase 2: scoping review of national health policies to identify contemporary MSK policy trends and foci. Phase 3: informed by phases 1-2, was a global eDelphi where multisectoral panellists rated and iterated a framework of priorities and detailed components/actions. Results Phase 1: 31 KIs representing 25 organisations were sampled from 20 countries (40% low and middle income (LMIC)). Inductively derived themes were used to construct a logic model to underpin latter phases, consisting of five guiding principles, eight strategic priority areas and seven accelerators for action. Phase 2: of the 165 documents identified, 41 (24.8%) from 22 countries (88% high-income countries) and 2 regions met the inclusion criteria. Eight overarching policy themes, supported by 47 subthemes, were derived, aligning closely with the logic model. Phase 3: 674 panellists from 72 countries (46% LMICs) participated in round 1 and 439 (65%) in round 2 of the eDelphi. Fifty-nine components were retained with 10 (17%) identified as essential for health systems. 97.6% and 94.8% agreed or strongly agreed the framework was valuable and credible, respectively, for health systems strengthening. Conclusion An empirically derived framework, co-designed and strongly supported by multisectoral stakeholders, can now be used as a blueprint for global and country-level responses to improve MSK health and prioritise system strengthening initiatives